The transcriptional enhancer factor-1 (TEF-1) family of transcription factors regulate tissue-specific gene expression in muscle and placenta. The mechanism whereby TEF-1 confers tissue specificity depends largely on the interaction of TEF-1 with tissue-specific cofactors. Transcription cofactor Vgl-4 (vestigial-like protein 4) is a 290 amino acid nuclear protein that interacts with TEF-1 and MEF-2. Vgl-4 is the only member of the vestigial-like family that is expressed in heart. Overexpression of Vgl-4 in cardiac myocytes interferes with basal expression and ?-adrenergic receptor-dependent activation of a TEF-1 dependent skeletal ?actin promoter. This suggests that Vgl-4 counteracts ?-adrenergic activation of gene expression in cardiomyocytes. There are two isoforms of Vgl-4 that are produced as a result of alternative splicing events.